Aging patients confined to wheelchairs by non-healing fractures were able to walk and live independently again following treatment with the osteoporosis drug teriparatide (Forteo), a preliminary study has found.
Research presented in February at the Orthopaedic Research Society meeting showed that out of 145 patients who had an unhealed bone fracture, half of them for six months or longer, 93 percent showed significant healing and pain control after being on teriparatide, a recombinant form of parathyroid hormone, for only eight to 12 weeks.
The findings persuaded the National Institutes of Health to fund a clinical trial in Rochester, and if the preliminary data are any indication, researchers just may have discovered a new, in-the-body stem cell therapy that can turbocharge the body’s natural bone healing process.
Out of around six million fractures in the U.S. each year, approximately 5% will have slow or incomplete healing. According to J. Edward Puzas, Ph.D., principal investigator of the clinical trial, at the University of Rochester Medical Center.
“In many people, as they get older, their skeleton loses the ability to heal fractures and repair itself,” Puzas said. “With careful application of teriparatide, we believe we’ve found a way to turn back the clock on fracture healing through a simple, in-body stem cell therapy.”
Particularly impacted are the nearly 60,000 Americans suffering from pelvic fractures. Bracing and immobilization in these cases are not an option, and the injury leaves people immobile and in pain before the bone fuses.
“It takes three to four months for a typical pelvic fracture to heal. But during those three months, patients can be in excruciating pain, because there are no medical devices or other treatments that can provide relief to the patient,” said Susan V. Bukata, M.D., medical director of the Center for Bone Health at the University of Rochester Medical Center. “Imagine if we can give patients a way to cut the time of their pain and immobility in half? That’s what teriparatide did in our initial research.”
Translational Medicine in Action
The research has its roots in Bukata’s clinic. It was there she noticed painful bone fractures in osteoporotic patients heal within a few months of taking teriparatide.
Bukata was also serving at the time on a research team at the University’s Center for Musculoskeletal Research. She started suggesting the team deploy its efforts in a different direction based on the results she was seeing with patients who were taking teriparatide.
“I had patients with severe osteoporosis, in tremendous pain from multiple fractures throughout their spine and pelvis, who I would put on teriparatide,” said Bukata. “When they would come back for their follow-up visits three months later, it was amazing to see not just the significant healing in their fractures, but to realize they were pain-free – a new and welcome experience for many of these patients.”
Puzas and Bukata decided to focus in both the lab and clinic to understand if what she had seen were coincidences or if there was an underlying process behind such life-changing results.
“While we had come to understand how teriparatide builds bone more robustly than the body can on its own, up to that point, we had no clue how the drug would or could help with fracture healing,” Puzas said.
Bukata began prescribing teriparatide to patients with non-healing fractures, and was amazed at her findings: 93 percent showed significant healing and pain control after being on teriparatide for only eight to 12 weeks. And in the lab, Puzas began to understand how teriparatide stimulates bone stem cells into action.
How Bones Heal
In a fracture, the bone becomes unstable and may move, creating painful micromotion. As the bone starts to heal, it must go through well-defined stages.
In the first phase, osteoclasts, cells that break down bone, clean up fragments and debris produced during the break.
Next, a layer of cartilage, callus, surrounds the fracture and then calcifies, preventing the bony ends from moving. This allows relief from the pain brought on by micromotion.
It is only after the callus is calcified that bone forming cells, osteoblasts, begin to function, replacing the cartilage layer with true bone. The osteoblasts ultimately reform the fracture to match the shape and structure of the bone into what it was before the break. Teriparatide considerably speeds up fracture healing, according to Puzas, changing the behavior and number of the cartilage and the bone stem cells in the process.
“As a result, the callus forms quicker and stronger. Osteoblasts form more bone and the micromotion associated with the fracture is more rapidly eliminated. All of this activity explains why people with non-healing fractures can now return to normal function sooner,” says Puzas.
“The decreased healing time is significant, especially when fractures are in hard-to-heal areas like the pelvis and the spine, where you can’t easily immobilize the bone – and stop the pain,” Bukata added. “Typically, a pelvic fracture will take months to heal, and people are in extreme pain for the first eight to 12 weeks. This time was more than cut in half; we saw complete pain relief, callus formation, and stability of the fracture in people who had fractures that up to that point had not healed.”
Clinical Implications for Bone Fractures
There are important clinical implications to the findings. Orthopaedists may soon have a new tool to deal with many common, painful bone ailments. Included are the tens of thousands of painful fractures for which there is no treatment; vertebral compression fractures, pelvic fractures, clavicle fractures, fractures that won’t heal, and fractures in patients that are either too sick to have surgery or chose not to have surgery.
“Many people don’t realize that pelvic fracture carries with them the same mortality as hip fractures – in one year, approximately one-quarter of all older women with pelvic fractures will die from complications,” Bukata said. “And during that year of recovery, a patient typically puts a greater strain on our health care system, not to mention their pain and suffering.”
Much more is at stake than comfort and pain relief. Patients who would otherwise be confined to nursing homes or require additional medical attention due to non-healing fractures might be able to live an independent life.
In the next stage of clinical research, the team will study post-menopausal women and men over 50 who come to the Emergency Department at Strong Memorial Hospital with a low-energy pelvic fracture. One group of patients offered teriparatide, the other a placebo, and both will be followed for 16 weeks to measure the fracture healing process in a variety of ways: pain levels, microscopic bone growth determined through CT scans and functional testing of bone strength, among others.
Teriparatide, manufactured by Eli Lilly and Co., was approved by the FDA in 2002 for the treatment of osteoporosis in men and postmenopausal women at high risk for having a fracture. The drug is also approved to increase bone mass in men with primary or hypogonadal osteoporosis who are at high risk for fracture.
Illustration: Scannign electron micrograph of osteoporotic bone, Credit David Gregory & Debbie Marshall, Wellcome Images